Friday, October 24, 2014

Transplant Decision

We found out that Laya is not a carrier of GM1 (Yay!) and she is a perfect match for Evan. Knowing this, it did make the decision a little harder. But, we have decided not to go with a Bone Marrow transplant for Evan.

Please note: I am not a scientist or doctor! The following is what I I've learned based on info from the doctors and case studies on the internet. We had to learn as much as we could about a whole different field, that's why it was hard to make the decision, we didn't feel we knew enough about it. 

We have a few main reasons for not doing the transplant
  1. We couldn't find any real evidence that doing a BMT would change the course of GM1. No guarantees, it would have been a gamble. We were initially hopeful about it, because of the success Bone Marrow transplants have had with Hurler's patients (MPS type I, a very similar diseases to ours has been able to maintain IQ over time!). But we also knew it didn't have much success, if any, with Tay Sachs disease, (GM2 Gangliosidosis). The studies we've found haven't changed the course of the disease and sometimes make the disease progress quicker. One article we found explained that GM1 Gangliosidosis works much more similarly to GM2 Gangliosidosis in the way it destroys brain cells.  MPS I seems to kill brain cells in a more round about way. (At least that's how I understand it) Once we came to that conclusion, we immediately decided not to do a BMT. We knew going into it, that everything would have to align perfectly for us to go through with a transplant. 
  2. It would have been very hard on Evan. He is at the height of his life right now. He is able to play, climb, get into everything :) and live a pretty normal life. As the course of the disease takes him, he will lose skills from here on out. It would not have been fun and he would have regressed quicker through the process and possibly would not be able to gain those skills back even if the transplant was "successful." 
  3. 10% chance he would die from the process or from complications by it. 
  4. Another 10% chance the transplant would not be successful and he would have do get another transplant. (At least I believe that's what they told me)
Note: If Evan had Hurler Syndrome, we probably would have done a Bone Marrow transplant, since Laya was such a perfect donor for him and he has not had much mental regression (if any) from the disease. There would be a strong hope of prolonging much better mental stability and learning ability. 

Clinical Trial offers some hope for us: 
We are hoping to be involved (Evan and Eli) in the clinical trial called Syner-G using the drug Zavesca along with the Ketogenic diet. There is the theoretical possibility that it will slow down the progression of the disease and possibly halt it for a time. None of that has been proven yet, so up to this point, it is still all speculative. 

Jeanine Utz at UMN has been working with our insurance. First they tried to just put the drug through, it didn't work and they wanted a prior authorization. The insurance then denied the prior-auth, so now the team is working on an appeal. She said they would have the appeal done by 10/28/14. So we'll see what happens. She indicated that this was completely normal and frankly it usually happens this way. We shall wait and see. 

As we were trying to decide about transplant, I looked around the internet to find some data on some of these BMTs. Here are some links we found. 

My conclusion: Overall success of BMT in Hurler Syndrome - MPS I

BMT in Hunter syndrome - MPS II My conclusion: it hasn't shown much success Neurologically

Little Bone Marrow success in Tay-Sachs, Sandhoff and GM-1

Three kids journey with TaySachs and BMT: This story can really freak you out if you are considering a transplant. I think the story is spun a certain direction, but the events are accurate.  - Overview of the story
Article from a parent of Dakota
Dakota at age 8 with her parents  - (Dakota lived to age 15, she died spring 2014, I believe.)

Animal Model
O'Brien et al. (1990) performed allogeneic bone marrow transplantation early in life in a case of canine GM1-gangliosidosis. Despite successful engraftment, no benefit was found. 

Substrate reduction therapy.


The therapeutic options for lysosomal storage diseases (LSDs) have expanded greatly over the past decade, although for many disorders there is still no effective treatment. Given that the majority of LSDs involve pathological changes in both the brain and peripheral tissues, effective treatment of central nervous system (CNS) and peripheral manifestations still remains a considerable technical challenge. Type 1 Gaucher disease has two approved treatment modalities - enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) - which have unique, independent and potentially complementary mechanisms of action. The availability of these two therapies has greatly increased the options for the effective clinical management of type 1 Gaucher disease. ERT involves the intravenous administration of fully functional enzyme that is taken up by cells and delivered to the lysosome, where it can compensate for the underlying enzyme deficiency. SRT uses an orally available, small molecule drug that inhibits the first committed step in glycosphingolipid biosynthesis. The aim is to reduce the rate of biosynthesis of glycosphingolipids to offset the catabolic defect, restoring the balance between the rate of biosynthesis and the rate of catabolism. SRT also has the potential to treat LSDs with CNS pathology, as the drug in clinical use (miglustat, Zavesca; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland) crosses the blood-brain barrier. In this review, the current status of SRT for the treatment of Gaucher disease and other LSDs will be discussed, based upon preclinical and clinical studies.


SRT is an oral alternative treatment option for patients with type 1 Gaucher disease unwilling or unable to receive ERT. With the recent reports of clinical improvement/stabilization of CNS manifestations following SRT in patients with Niemann-Pick disease type C, miglustat may also have a role to play in the management of patients with glycosphingolipid storage in the brain. Furthermore, as SRT synergises with other therapeutic modalities, it may also prove to be a key component of combination therapies in the future.
Status at Minoryx

Through its proprietary technological platform (SEE-Tx), Minoryx has identified a novel series of non-competitive pharmacological chaperones which are able to stabilize GLB1 and restore its enzymatic activity.

These compounds are binding on a novel site identified through SEE-Tx and contrary to pharmacological chaperones targeting the active site, they do not inhibit GLB1. Also, Minoryx has established collaborations with many of the academic groups leading research on this field.
Currently the project is at lead optimization and a development candidate is expected in the following months. Such compound would be a first-in-class drug for the treatment of GM1-glangliosidosis and/or Morquio B diseases.